Search results for "Drug metabolism"
showing 10 items of 103 documents
In vitro assessment of competitive and time-dependent inhibition of the nevirapine metabolism by nortriptyline in rats
2018
Abstract Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it is inexpensive, readily absorbed after oral administration and non-teratogenic. In the present work, the mechanism of a previously described pharmacokinetic interaction between NVP and the antidepressant drug nortriptyline (NT) was studied using rat hepatic microsomes. The obtained results showed a competitive inhibition of the NVP metabolism by NT. The three main NVP metabolites (2-OH-NVP, 3-OH-NVP and 12-OH-NVP) where competitively inhibited with similar inhibitory constant values (Ki …
Effect of some indole derivatives on xenobiotic metabolism and xenobiotic-induced toxicity in cultured rat liver slices.
1999
In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague-Dawley rats. While treatment of rat liver slices for 72 hours with 2-200 microM of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 microM 3,3'-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears…
Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO).
2002
Tresperimus (Cellimis), a new immunosuppressive agent, is mainly eliminated in the rat through metabolism, in which the oxidative deamination of the primary amine of the drug plays a major role. We have previously demonstrated in vivo the significant involvement of semicarbazide-sensitive amine oxidase (SSAO) in this reaction. Rat aorta, a tissue with one of the highest specific SSAO activities, was tested as a new in vitro model to elucidate tresperimus metabolism, using a combination of liquid chromatography/mass spectrometry (LC/MS) and high-performance liquid chromatography (HPLC) analyses. The metabolites resulting from the main metabolic pathway of the drug were formed in rat aorta ho…
Odorant metabolism catalyzed by olfactory mucosal enzymes influences peripheral olfactory responses in rats.
2013
International audience; A large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in mammalian olfactory mucosa (OM). These enzymes are known to catalyze the biotransformation of exogenous compounds to facilitate elimination. However, the functions of these enzymes in the olfactory epithelium are not clearly understood. In addition to protecting against inhaled toxic compounds, these enzymes could also metabolize odorant molecules, and thus modify their stimulating properties or inactivate them. In the present study, we investigated the in vitro biotransformation of odorant molecules in the rat …
A Method for the Cryopreservation of Liver Parenchymal Cells for Studies of Xenobiotics
1993
Abstract An optimized computer-controlled freezing protocol for the cryopreservation of rat liver parenchymal cells was developed. The best survival rates were obtained when a slow cooling rate was used and when the supercooling was interrupted with a shock cooling to initiate ice nucleation. Ten percent dimethyl sulfoxide was added and removed gradually for best results. Thawed rat liver parenchymal cells had a viability, as judged by trypan blue exclusion, of 69% (SD = 6) versus 82% (SD = 7) for freshly isolated cells. The content and activities of the xenobiotic metabolizing enzymes, cytochrome P450. UDP-glucuronosyl transferase, and microsomal and cytosolic epoxide hydrolase, were not a…
Effect of nitrite on microsomal cytochrome P-450.
1978
1. Addition of nitrite to anaerobic rat liver microsomes leads to the appearance of a difference spectrum similar to the spectrum of the ferrous cytochrome P-450-NO complex. A Soret band is found at 444 nm in phenobarbital-stimulated microsomes but at 442 nm in 3-methylcholanthrene-stimulated microsomes. An alpha-band is located at 583 nm in both types of microsome. 2. The initial nitrite-induced difference spectrum is converted into a spectrum lacking a Soret band but with a prominent absorbance minimum at 417 nm. This is more rapid in microsomes from phenobarbital-treated animals where it is completed in 8 min than in microsomes from 3-methylcholanthrene-treated animals. A similar spectru…
Ethoxyquin as an inducer and inhibitor of phenobarbital-type cytochrome P-450 in rat liver microsomes.
1977
Abstract The effect of ethoxyquin in vivo and in vitro on drug metabolism in rat liver microsomes was studied. In feeding experiments, a threshold dose of induction was found at 0.05% ethoxyquin for 14 days. At 0.5% ethoxyquin, relative liver weight, cytochrome P-450 content, cytochrome b5 content, ethylmorphine demethylation, and ethoxycoumarin deethylation were increased by a factor of 1.5 to 2. Aryl hydrocarbon hydroxylase activity was, however, not induced but even decreased by 0.5% ethoxyquin in food. Induction of epoxide hydratase was marked, amounting to 400% of control after 0.5% ethoxyquin. The induced enzyme was similar to the phenobarbital-inducible cytochrome P-450 in its CO spe…
Coffee and its chemopreventive components Kahweol and Cafestol increase the activity of O6-methylguanine-DNA methyltransferase in rat liver—compariso…
2003
Abstract A lower rate of colon cancer was observed in consumers of coffee with a high content of the diterpenes Kahweol and Cafestol (K/C). In animal models, K/C have been found to protect against the mutagenic/carcinogenic effects of compounds such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), aflatoxin B1, and 7,12-dimethylbenz[a]anthracene. Thus far, such chemoprotection by K/C has been attributed to modifications of xenobiotic metabolism, e.g. enhanced detoxification by UDP-glucuronosyltransferase (UDPGT) and/or glutathione transferase (GST). In the present study, we investigated the potential of several coffee-related treatments (K/C [1:1], Cafestol-alone, Turkish coffee) …
Metabolism of apigenin by rat liver phase I and phase II enzymes and by isolated perfused rat liver
2004
The metabolism of apigenin, a low estrogenic flavonoid phytochemical, was investigated in rat using liver models both in vitro (subcellular fractions) and ex vivo (isolated perfused liver). In vitro, phase I metabolism led to the formation of three monohydroxylated derivatives: luteolin which was the major metabolite (K(m) = 22.5 +/- 1.5 microM; V(max) = 5.605 +/- 0.090 nmol/min/mg protein, means +/- S.E.M.), scutellarein, and iso-scutellarein. These oxidative pathways were mediated by cytochrome P450 monooxygenases (P450s). The use of P450 inhibitors and inducers showed that CYP1A1, CYP2B, and CYP2E1 are involved. In vitro studies of phase II metabolism indicated that apigenin underwent co…
Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode.
1975
1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of su…